Abstract P2-03-16: Quantifying estrogen and progesterone receptor status in early-stage invasive lobular carcinoma of the breast: associated factors and outcomes in an institutional series
Authors: Elle Clelland, Harriet T. Rothschild, Anne Patterson, Julissa Molina-Vega, Mandeep Kaur, Mary Kathryn Abel, W. Fraser Symmans, Jo Chien, Christopher J. Schwartz, Rita Mukhtar
Journal: Cancer Research (2023)

Abstract Background: Recent guidelines regarding estrogen (ER) and progesterone (PR) receptor testing from the American Society of Clinical Oncology and College of American Pathologists defined a new reporting category of ER-low positive breast cancer for tumors with 1-10% ER expression by immunohistochemistry (IHC). The clinical implications of ER-low positivity are incompletely understood, especially in invasive lobular carcinoma (ILC), the second most common type of breast cancer. Given the rarity of low-ER positivity in ILC, we evaluated tumor features and outcomes associated with a spectrum of ER/PR positivity in a monoinstitutional ILC cohort. Methods: We analyzed cases of stage I-III ILC with available IHC reports. Based on prior published categories in ILC, we classified ER as low, medium, or high as defined by ER staining of 10–69%, 70–89%, and ≥90% respectively. PR negative, low, and high tumors were defined by 0%, &amp;lt; 20%, or ≥20% staining respectively. We used chi-squared tests, t-tests, and Cox proportional hazards models in Stata 16.1 to evaluate associations between ER/PR categories including clinicopathologic variables and event-free survival (EFS). Results: Of 744 cases, 24 (3.2%) were ER negative and 10 (1.3%) were ER-low positive as defined by 1-10% positive staining. 713 remaining cases had ER positivity ≥ 10% and comprised the cohort categories of ER low, medium, and high for this study (11.2%, 15.0%, and 73.8% respectively). In 751 cases with PR data, 122 (16.2%) were PR negative, 145 (19.4%) were PR low and 483 (64.3%) were PR high. ER high status was significantly associated with older age (mean 56.7, 56.7, and 60.6 years in ER low, medium, and high respectively, p=0.0005). ER low was associated with PR negative and low status (42.3% were PR neg/low and ER low, versus 37.4% with ER medium and 29.9% in ER high, p=0.045), and more likely to have overexpression of HER2 (9.7%, 9.0%, and 2.9% ER low, medium, high, respectively, p=0.002). ER low tumors were more likely to be grade 1 than ER medium or high (41.8%, 29.8% and 24.5% respectively, p=0.025), and have positive surgical margins (39.4%, 35.9% and 23.9% respectively, p=0.002). ER status was not associated with Ki67, stage, body mass index (BMI), lymphovascular invasion, lobular carcinoma in situ (LCIS), pleomorphic histology, local therapy, or chemotherapy use. In contrast, PR high was significantly associated with younger age (57.6 versus 63.5 years in PR low, p&amp;lt; 0.0001). PR low was associated with HER2 overexpression (8.6% versus 3.2% in PR high, p=0.002). PR low cases were more likely to present at higher stages (15.8% stage III versus 10.1% stage III in PR high, p=0.032), to be pleomorphic (16.8% versus 8.2%, p&amp;lt; 0.001), and to receive chemotherapy (30.8% versus 23.1%, p=0.022) but were less likely to have associated LCIS (64.0 versus 74.2%, p=0.004). PR status was not associated with Ki67, BMI, lymphovascular invasion, local therapy, or surgical margins. In a Cox proportional hazards model adjusting for age, stage, grade, pleomorphic histology, and chemotherapy use, ER category was not associated with EFS but both PR negative and PR low status each had significantly worse EFS compared to PR ≥20% (HR 3.5, 95% CI 1.8-6.7, p&amp;lt; 0.001 for PR negative, and HR 2.0, 95% CI 1.1-3.5, p=0.015 for PR low). The estimated cumulative 5-year EFS for patients with ER low, medium, and high tumors was 87.1%, 93.4%, and 90.1% respectively. The estimated cumulative 5-year EFS for patients with PR negative, low, and high tumors was 78.9%, 90.2%, and 92.7% respectively. Conclusions: Using ILC-specific categories for ER expression, we found associations between ER category and clinicopathologic variables but not with EFS. In contrast, PR negative and low status was associated with worse EFS. These findings highlight the importance of exploring the spectrum of ER/PR activity within ILC, a classically strongly hormone receptor-positive tumor type, using more quantitative methods. Citation Format: Elle Clelland, Harriet T. Rothschild, Anne Patterson, Julissa Molina-Vega, Mandeep Kaur, Mary Kathryn Abel, W. Fraser Symmans, Jo Chien, Christopher J. Schwartz, Rita Mukhtar. Quantifying estrogen and progesterone receptor status in early-stage invasive lobular carcinoma of the breast: associated factors and outcomes in an institutional series [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-03-16.